Apparatus for dry sterilization of medical devices and materials

ABSTRACT

A process for dry sterilization of medical devices and materials in which these materials are subjected to an electrical discharge in a gaseous atmosphere to produce an active plasma for surface sterilization of the devices and materials.

This is a division of application Ser. No. 019,134, filed Feb. 25, 1987,now U.S. Pat. No. 4,801,427.

BACKGROUND OF THE INVENTION

Modern medical practice requires the use of aseptic materials anddevices, many of them meant for repeat use. In order to achieve thissterilization, processes are needed, at the manufacturer, and also atthe hospitals for treatment of reusable materials and devices.

Typical of materials which are reused in the hospital environment andrequire repeated sterilization are major surgical instrument trays,minor surgical kits, respiratory sets, fiber optics, scopes and breastpumps.

There are a wide variety of medical devices and materials that are to besupplied from the manufacturer already packaged and sterile. Many ofthese devices and materials are disposable. Typical of this group arebarrier packs, head coverups and gowns, gloves, sutures and catheters.

One major sterilization process in present use is that which employsethylene oxide (EtO) gas at up to three atmospheres of pressure in aspecial shatter-proof sterilization chamber. This process, in order toachieve effective asepsis levels, requires exposure of the materials tothe gas for at least one hour followed by a minimum of twelve hours, orlonger, aeration period. The initial gas exposure time is relativelylong because the sterilization is effected by alkylation of amino groupsin the proteinaceous structure of any microorganism. EtO sterilizationrequires the attachment of the entire EtO molecule, a polyatomicstructure containing seven atoms to the protein. This is accompanied bythe requirement of hydrogen atom rearrangement on the protein to enablethe attachment of EtO. Because of the space factors governing theattachment of such a bulky molecule, the process needs to be carried outat high pressure and be extended over a long period of time. It is,therefore, deemed very inefficient by the industry at large.

Perhaps the chief drawback to this system, however, is its dangeroustoxicity. Ethylene-oxide (EtO) is a highly toxic material dangerous tohumans. It was recently declared a carcinogen as well as a mutagen. Itrequires a very thorough aeration process following the exposure of themedical materials to the gas in order to flush away EtO residues andother toxic liquid by-products like ethylene glycol and ethylenechlorohydrin. Unfortunately, it is a characteristic of the gas and theprocess that EtO and its toxic by-products tend to remain on the surfaceof the materials being treated. Accordingly, longer and longer flushtimes (aerations) are required in order to lower the levels of theseresidues absorbed on the surface of the materials to a safe operationalvalue. A typical volume for each batch using this EtO process is 2 to 50cu. ft. within the health care environment.

A number of other approaches for performing sterilization have also beenemployed. One such process is steam autoclaving. However, this requireshigh temperature and is not suitable for materials which are affected byeither moisture or high temperature. Another approach utilizes eitherx-rays or radioactive sources. The x-ray approach is difficult andexpensive. The use of radioactive sources requires expensive wastedisposal procedures, as well as requiring radiation safety precautions.The radiation approach also presents problems because ofradiation-induced molecular changes of some materials, which, forexample, may render flexible materials brittle.

It is therefore a primary object of the present invention tO provide aprocess and apparatus for dry sterilization of medical devices andmaterials, which can be operated efficiently, both with respect to timeand volume.

It is another object of the present invention to provide a safe,nontoxic, process for the sterilization of medical devices andmaterials, a process which does not employ toxic feed gases and onewhich does not yield toxic adsorbed surface residues.

SUMMARY OF THE INVENTION

Broadly speaking in the present invention, sterilization is achieved byexposing the medical devices and materials to a highly reducing gasplasma like that generated by gas discharging molecular hydrogen, or toa highly oxidizing gas plasma, for example, one containing oxygen. Thisplasma is generated by creating an electrical discharge in a gaseousatmosphere within an active zone within which the materials to besterilized are placed.

Generation of gas plasmas is a very well developed art, which has beenspecifically employed in semi-conductor processing. See, for example,U.S. Letters Pat. Nos. 3,951,705; 4,028,155; 4,353,777; 4,362,632;4,505,782 and RE 30,505.

In one instance the gas plasma sterilization process of this inventioninvolves evacuating a chamber to a relatively low pressure after thedevices or materials to be sterilized have been placed within it. Anoxidizing gaseous atmosphere is then provided to the chamber at arelatively low pressure, typically in the range 10 microns Hg to 10torr, corresponding to a gaseous flow rate range of 20 to 1000 standardcc per minute. An electrical discharge is produced within the chamber byconventional means, such as a microwave cavity or a radio frequency (RF)excited electrode. Alternatively, RF power in the power density range0.0125-0.05W/cm³ may be coupled into the oxidizing gas via a singleelectrode disposed within the chamber in a nonsymmetrical electricalconfiguration, or via two electrodes contained within the chamber in anelectrically symmetrical configuration. In either case the material tobe sterilized is placed on one of the electrodes, while he chamber'swall is maintained at ground potential. The resultant discharge producesa gas plasma including both excited electrically charged gaseous speciesand excited electrically neutral gaseous species. For example, freeradicals of atomic oxygen as well as excited molecular oxygen are formedin a discharge through molecular oxygen. These oxygen-bearing activespecies interact with the proteinaceous components of the microorganismsresiding on the surfaces of medical devices to be sterilized, denaturingthe proteinaceous molecules and achieving kill rates of microorganismsequivalent to a probability of survival of only one in a million.

The efficiency of this process is due, in part, to the fact that theactive plasma entities are atomically small (usually monoatomic ordiatomic) and therefore exhibit an enhanced ability to attach themselvesto a proteinaceous structure and/or abstract (remove) hydrogen atomsfrom it. The space restriction for this type of interaction is at leastone thousand times lower than that for EtO alkylation.

Several specific types of interaction take place. One specificinteraction is hydrogen abstraction from amino groups. Another isrupturing ring structures, particularly those including nitrogen, orcarbon-carbon bond cleavage. It is important to note that theseprocesses produce only gaseous effluents, such as water vapor and carbondioxide, which would not remain adsorbed on the surface of medicaldevices, but would be carried away from such devices with the main gasstream to the pump.

This sterilization process may be used with pre-packaged materials, suchas disposable or reusable devices contained within polyethylene oranother gas-permeable package. With polyethylene or Tyvek packaging, thebarrier wall of the package is pervious to the relatively small activespecies of the sterilizing plasma, but impervious to the largerproteinaceous microorganisms. (Tyvek is a bonded polyolefin produced byDuPont).

After evacuation of the chamber, and introduction of the gas or gasmixture, the gas(es) will permeate the package wall with a dynamic freeexchange of gas(es) from within and from outside the package. Uponstriking a microwave or an RF discharge to form the plasma, and,depending upon electrical configuration, the discharge may either beformed throughout the volume of the chamber, so that plasma is actuallyalso created within the package or, alternatively, the package may beplaced in an electrically shielded (field-free) glowless zone so that itis subject to predominantly electrically neutral active species whichpass through the packaging wall to interact with the surface of thematerials it contains.

In yet a different electrical configuration, the packages containingdevices to be sterilized can be placed on a conveyor belt and swept intoan atmospheric pressure corona discharge gap operated in ambient air.With this configuration, the discharge electrodes are comprised of agrounded conveyor belt forming the bottom electrode, while the topelectrode is comprised of a metal block with multiple needle-likenozzles for the dispersion of gas. Sterilization with this continuous,in-line, apparatus, is brought about by ozone formation, due to presenceof discharged oxygen in air, or due to any other oxidizing gas mixturethat can be introduced into the discharge gap via a plurality ofnozzles, which are an integral part of the top electrode. This coronadischarge will normally operate in the power density range 5-15 W/cm²and in the frequency range 10-100 KHz and 13-27 MHz, associated with gasflows in the range of several standard liters per second.

In order to enable device sterilization by a strongly oxidizing plasmawhen employing the process with for example polyethylene packaging, itis necessary to provide that oxygen-bearing active species can permeatethrough a typical organic package barrier (like that of a polyethyleneplastic pouch) in the first place, and that a sufficient number of thesespecies traverse that barrier in order to effectively kill allmicroorganisms on a medical device enclosed within the pouch. Relevantoxidizing species can be obtained by plasma discharging diatomic gaseslike oxygen, nitrogen, halogens, or binary mixtures of oxygen andhydrogen, oxygen and nitrogen, oxygen and inert gases, or the gaseouscombination of oxygen, nitrogen and inert gases like helium or argon.The predominance of oxygen in the above mixtures is preferred but notmandatory. A predominance of nitrogen, for example, will result inhigher process temperatures during sterilization for a given reactionpressure and power density. The inert gas fraction can be variable inthe range 10 to 95%; the higher the fraction, the lower the processingtemperature for a given pressure and power density. However,sterilization exposure time increases the higher the inert gas fractionin the mix. Substitution of argon for helium, for example, will resultin higher sterilization temperatures for a given pressure and powerdensity. In this case, instability of the gas discharge operation mayset in, requiring a power density increase at a given pressure, comparedto that employed with helium, resulting in higher process temperatures.

Effective sterilization can also be obtained with a pure reducinghydrogen plasma due to its very strong hydrogen atom abstraction(removal) capabilities from proteinaceous structures of microorganisms.Hydrogen in its mixtures with either nitrogen or oxygen, or with both,in the presence or absence of an inert gas, will show effectivesterilization capabilities over a wide range of concentrations in thesemixtures.

The first objective of facilitating the gaseous permeation through anorganic barrier is accomplished by evacuating the chamber (containingthe loaded pouches) to a base pressure of approximately 20 microns Hg.This rids the pouches of previously entrapped atmospheric air, andequalizes the pressure inside the pouch to that inside the chamber(across the organic barrier). The subsequent introduction into thechamber of an oxygen-containing gas, in a typical situation, willestablish an instantaneous higher pressure inside the chamber (outsidethe pouch) relative to that inside the pouch. This pressure gradientacross the pouches' barrier will serve as the initial driving force ofgas into the pouch. At an equilibrated state, an active and ongoinginterchange of molecules across the barrier will take place, at alltimes attempting to maintain the same pressure on both sides of theorganic barrier. Upon striking a discharge through this gas,oxygen-bearing active species will be generated. Typically these activespecies will be deactivated in large amounts by the organic barrier.This will commonly substantially reduce the availability of these activespecies to do the sterilizing job.

Therefore, in order to accomplish the second objective of generating asufficient number of oxidizing species traversing the organic barrier ofa package, the organic barrier must be passivated in such a way as tosubstantially reduce its take-up of oxygen-bearing active species neededas a sterilizing agent and which must render a final non-toxic medicaldevice, without the formation of any toxic by-products.

One such passivation method consists of simultaneously introducing intothe chamber a gaseous mixture, which in addition to oxygen-containinggas(es), also contains selected other gases as set forth below:

1. Organohalogens, based on carbon and/or silicon, attached to any ofthe known halogens. Particularly those organic compounds of carbonand/or silicon that are saturated or unsaturated and contain in theirmolecular structures one (1) or two (2) carbon or silicon atoms attachedto: a predominance of fluorine atoms; a predominance of chlorine atoms;a predominance of bromine or iodine atoms; an equal number of fluorineand chlorine atoms simultaneously; an equal number of chlorine andbromine atoms simultaneously; an equal number of fluorine and bromineatoms simultaneously; an equal number of fluorine and iodine atomssimultaneously; an equal number of chlorine and iodine atomssimultaneously. A predominance of fluorine in these compounds includesstructures where all other atoms attached to a carbon or a silicon atomcan be all the other halogens, or only one or two other halogens out ofthe four halogens known, in conjunction with other atoms, as for examplehydrogen. The same comments apply to a predominance of chlorine, bromineand iodine. For the latter, however, the simultaneous presence ofbromine is unlikely to be practical due to a low volatility of thestructure, but the simultaneous presence of fluorine or chlorine, orboth, is practical. It is worth noting that hydrogen-containingorganohalogens will have a tendency to polymerize under plasmaconditions, and in some cases, be flammable in as-received condition.

Most effective sterilizing mixtures of oxygen and an organohalogen arethose where the organohalogen is a mixture of organohalogens in itself,either based on carbon and/or silicon, where the oxygen fraction is over70% by volume; yet sterilization will be effected for lower oxygencontent at the expense of excessive halogenation of the surface of thematerial to be sterilized, and at the expense of excessive loss oftransparency of the wrapping pouch.

2. Organohalogens in conjunction with either nitrogen or an inert gaslike helium or argon. In these cases, it is considered practical to keepthe fraction of the inert gas in predominance in order to keep theprocess temperature as low as possible. Inert gas fractions up to 95% byvolume will be effective in killing microorganisms. The nitrogenfraction is ideally kept below that of the oxygen fraction.

3. Inorganic halogens, defined as compounds not containing carbon orsilicon, but preferably containing as the central atom or atoms eitherhydrogen, nitrogen, sulfur, boron, or phosphorus linked to any of theknown halogens in a similar manner as described for the organohalogensunder item 1 above, or defined as compounds that contain only halogenswithout a different central atom, like for example molecular halogens(e.g., F₂, C1₂) and the interhalogens which contain two dissimilarhalogen atoms (e.g., C1-F, I-F, Br-C1 based compounds, etc.). Also inthis case the inorganic halogen maybe, in itself, a mixture of differentinorganic halogens as defined above.

Most effective sterilizing mixtures of oxygen and an inorganic halogenare those where the oxygen fraction is over 80% by volume; yetsterilization will be effected for lower oxygen content at the expenseof excessive halogenation of the surface of the material to besterilized, and at the expense of excessive loss of transparency of thewrapping pouch.

4. Inorganic halogens in conjunction with either nitrogen or an inertgas as described in item 2 above.

5. Inorganic oxyhalogenated compounds, not containing carbon or silicon,but preferably contain either nitrogen, phosphorus, or sulfur, each ofwhich is simultaneously attached to oxygen and a halogen (e.g., NOC1,SOC1₂, POC1₃, etc.). More specifically, the nitrogen-oxygen, or thesulfur-oxygen, or the phosPhorus-oxygen entities in the previousexamples are linked to any of the known halogens in a similar manner asdescribed for the organohalogens under item 1 above. The inorganicoxyhalogenated fraction may be, in itself, a mixture of differentinorganic oxyhalogenated compounds as defined above.

Most effective sterilizing mixtures of oxygen and an inorganicoxyhalogenated structure are those where the oxygen fraction is over 70%by volume; yet effective sterilization will be obtained for lower oxygencontent at the expense of excessive halogenation of the surface to besterilized, and at the expense of excessive loss of transparency of thewrapping pouch.

6. Inorganic oxyhalogenated compounds in conjunction with free nitrogenor an inert gas as described in item 2 above.

7. Multicomponent mixtures comprised of members in each of theaforementioned groups. The simultaneous presence of free nitrogen and aninert gas like helium or argon in any of the above mentioned groups, orin multicomponent mixtures comprised of members in each of theaforementioned groups, will also be effective in killing microorganisms.The free nitrogen fraction should be ideally below that of oxygen inorder to maintain a lower reaction temperature.

More specific and relatively simple multicomponent mixtures that areeffective sterilants as well as effective organic barrier passivationagents are listed below:

    ______________________________________                                        Specific Multicomponent Mixtures Comprised of                                 Fractions A + B (percent of fraction is by volume)                            Fraction A           Fraction B                                               ______________________________________                                        O.sub.2 (92-97%)     CF.sub.4 (3-8%)                                          [O.sub.2 (40%)--He(60%)]                                                                           CF.sub.4 (0.25-3%)                                       [O.sub.2 (8%)--CF.sub.4 (92%)]                                                                     He(80%)                                                  [O.sub.2 (17%)--CF.sub.4 (83%)]                                                                    He(80%)                                                  [O.sub.2 (83%)--CF.sub.4 (17%)]                                                                    He(80%)                                                  [O.sub.2 (92%)--CF.sub.4 (8%)]                                                                     He(80%)                                                  ______________________________________                                    

Many of the aforementioned gas mixtures are, in themselves, novelchemical compositions.

The plasma discharge through such a composite mixture will, for example,create both oxygen-bearing and fluorine, or chlorine-bearing activespecies simultaneously. The latter will predominantly be responsible forpassivating the organic barrier, since fluorination or chlorination,rather than oxidation of the organic barrier is favoredthermodynamically. Therefore, the take-up of fluorine orchlorine-bearing active species by the organic barrier of the pouch willbe preferential. This will leave a relatively larger fraction ofoxygen-bearing active species available for sterilization, since thelatter cannot easily be taken up by a fluorinated or chlorinatedsurface.

In addition, sterilization by oxygen-bearing active species is aided,for example, by simultaneously discharging an oxygen-containing andfluorine or chlorine containing gas residing inside the enclosing pouch.This gas had previously permeated through the organic barrier prior tothe commencement of the discharge. The plasma, which is generated withinthe pouch, much in the same way as previously described for the plasmagenerated within the chamber, will create active species that containboth oxygen and fluorine or chlorine within the pouch directly. Aspreviously described, the competition for take-up by the organic barrier(pouch) will be won by the fluorinating or chlorinating species, leavinga larger net concentration of active species containing oxygen to do aneffective sterilizing job.

However, residual fluorine or chlorine-bearing active species within thepouch and not up-taken by it will also perform effective sterilization,since they are strongly chemically oxidizing agents. But, the fractionof fluorine or chlorine-containing gas in the original composite gaseousmixture, is substantially smaller than the oxygen-containing component.Thus, a major portion of microorganisms kill will be attributed to theoxygen-bearing species in the plasma. In either case, however, the endresult is a continuous attack on the proteinaceous structure of themicroorganism resulting in its degradation and fragmentation intogaseous products. This chemical action by the reactive plasma is toinitially modify (denature) the proteinaceous network of themicroorganism, disrupting its metabolism at a minimum, but more commonlyimpeding its reproduction.

DESCRIPTION OF THE DRAWINGS

In the drawing FIG. 1 is a general diagrammatic illustration of anapparatus suitable for use in the practice of this invention;

FIG. 2 is a cross-sectional view of a sterilization chamber for use inthe practice of the invention;

FIG. 3 is a cross-sectional view of another embodiment of a sterilizatonchamber for use in the practice of the invention;

FIG. 4 is a side view of the apparatus of FIG. 3; and

FIGS. 5, 6, 7, 8 and 9 are cross sectional views of alternativeembodiments.

DESCRIPTION OF PREFERRED EMBODIMENTS

FIG. 1 is a general diagrammatic illustration of an RF excited dischargechamber of the type used in the process of this invention. Thecylindrical chamber 11 is formed, in this instance, of glass or quartzand encloses within it the material 14 to be treated. The chamber iscommonly connected to a mechanical vacuum Pump (not shown) thatestablishes sub-atmospheric pressure conditions within the chamber. Anexciter coil 12 couples RF energy from RF source 13 to the gas enclosedwithin the gas tight chamber creating a plasma therein.

Alternatively, a microwave discharge cavity operating at 2450 MHz mayreplace the RF exciter coil to couple power into the gas. With asuitable selection of a reducing gas, like hydrogen, or an oxidizinggas, such as oxygen, as a typical example, a discharge may be initiatedand maintained within the chamber. In the gas plasma formed by thatdischarge a number of excited species, both molecular and atomic, areformed. The interaction of these species with a surface of the device ormaterial to be sterilized accomplishes the sterilization in the mannerdescribed above. The time duration of the process needed to achievesatisfactory sterilization will vary with other parameters of thedischarge such as gas flow, pressure, RF power density, and load size.

In one physical embodiment the apparatus may include an inner perforatedmetallic cylinder mounted generally concentric with the long axis of thechamber to form within the perforated cylinder a glowless, field-freezone. In FIG. 1 a perforated cylindrical shield 15 of this type is shownin dotted lines.

When, as illustrated in FIG. 2, a microwave energy source 18 at 2540MHz. is employed in lieu of the RF generator 13, the perforated metalliccylinder cannot be mounted concentric about the long axis of thechamber. Instead, the microwave cavity 16 is mounted at one end ofchamber, 11, and a perforated, metallic shield 17 may be placed justbeyond it toward the opposite end of the chamber, spanning the entirediameter cross section of the chamber, thus creating a field-free andglowless reactive zone immediately below it and away from the microwavecavity. These arrangements permit material 14 placed within this zone tobe generally isolated from electrically charged species, while allowingthe electrically neutral reactive plasma species, such as oxygenradicals, to interact with the surface of the material to be sterilized.In this manner, sterilization is commonly effected at lower processtemperatures.

In the most preferred embodiments the chamber is formed of a metal outershell with either a single internal perforated cylindrical shield, orperhaps With two such metallic shields, the RF energy being coupled, inthis latter configuration between the two conducting perforatedcylinders. In either case, the discharge glow is confined to the spacebetween the inner wall of the chamber and the surface(s) of theperforated cylinder(s), leaving the work volume defined by the innerperforated cylinder field-free, void of the plasma glow, and at arelatively low operating temperature. With a microwave cavity replacingthe RF energy source, a single metallic perforated shield can be usedand placed just below the cavity in accordance with the operationaldescription given for FIG. 2.

One such chamber configuration is illustrated in FIGS. 3 and 4. Thecylindrical outer wall 21, typically formed of aluminum or stainlesssteel, is maintained at ground potential and serves as the chamberenclosure. Suitable dimensions for this chamber are a diameter of 36"and a length of 48". A metallic perforated inner cylinder 23 is mountedon insulating spacers 29 within the chamber so that it is positionedgenerally parallel with the long axis of the outer wall 21 of thechamber. These spacers may be formed of any suitable non-reactive andinsulating type of material such as ceramic. The cylinder perforationsare typically 2.5 mm diameter holes spaced in all directions from oneanother by approximately 0.5 cm in a triangulated manner. Longitudinalsupport rails 27 are fastened to the inner wall of the perforatedcylinder 23 to support a wire basket 25 in which the materials anddevices to be sterilized are placed. A suitable RF source 22 is coupledbetween the grounded outer chamber wall 21 and the perforated innercylinder 23. Usually this RF source should be capable of producing an RFoutput in the range 0.0125 to 0.05 W/cm³ at frequencies in the 10-100kilohertz or 13-27 megahertz range.

As illustrated in FIG. 4, an evacuation port 31 at the end of cylinder21 is connected to a pump (not shown) and provides for suitableevacuation of the chamber. The gas supplied for the discharge isgenerally flowed through the chamber by means of perforated diffusiontubes 35. Alternately, gas may be introduced into the chamber via a gasdispersion device (not shown) mounted behind chamber door 39 from theinside.

Material to be sterilized may be placed within wire basket 25 resting onrail 27 through the entry port behind chamber door 39. Chamber door 39may be any suitable closure that can be conveniently opened and closedand left in a sealed position during evacuation and the gas dischargeoperation.

FIG. 5 illustrates a second preferred embodiment of the apparatus forpracticing the process of the invention. In this configuration, theouter chamber wall 21 is again formed of metal, such as aluminum orstainless steel and is electrically grounded and of similar dimensionsto that illustrated in FIG. 3. Mounted within the chamber is an innerconcentric cylinder 43 formed of a perforated metal and supported oninsulating support struts 46. The spacing between the inner wall of thechamber and the perforated interior cylinder may range typically from 10to 17 cm where the chamber has an I.D. of 36". A second metallicperforated cylinder 41 is concentrically mounted intermediate betweenthe inner perforated cylinder 43 and the inner wall of the chamber. Thissecond perforated cylinder is supported on insulating struts 47 and isspaced typically 4 to 7 cm away from the inner perforated cylinder 43.The insulator struts may again be formed of a ceramic material. Mountedon the interior of the inner concentric cylinder 43 are support rails 27for carrying a wire basket which would contain the materials to besterilized. Both the outer chamber wall 21 and the inner perforatedcylinder 43 are electrically connected to point of potential reference(ground). Electrical connections would most usually be made throughceramic seal feedthroughs 48 and 49. The intermediate cylinder 41 iselectrically connected to one side of the RF power supply 22, the otherside of which is connected to the point of potential reference.

While a variety of conventional RF sources may be used, the most typicalvalue for the RF frequency is 13.56 MHz or, alternatively, 10-100 KHz.As in the embodiment of FIG. 4 longitudinally extending gas diffusiontubes 35 may be employed to provide the gas to the interior of thechamber. Typically each tube would have holes of diameter between 0.5and 1.5 mm, spaced approximately 1" apart along its length. The holediameters closer to the gas source would be of the smaller diameter.Alternatively, gas inlets may be provided behind door 39 . As indicatedin embodiments of FIGS. 3, 4 and 5 the perforated inner cylinders may beopen-ended at both ends or, may be closed with the same perforated stockas is used to form the cylinder(s). The sterilization chambers describedin FIGS. 3, 4 and 5 may be connected to a microwave discharge source,typically operating at 2540 MHz, in lieu of an RF energy source. In thiscase, the concentric perforated metallic cylinder(s) may be replaced bya single perforated shield in accordance with the operationaldescription given for FIG. 2.

FIG. 6 illustrates a third preferred embodiment of the apparatus forpracticing the process of the invention. In this diagrammaticdescription the outer chamber wall 21 is again formed of metal, such asaluminum or stainless steel, and is of similar dimensions to thatillustrated in FIG. 3. Mounted within the chamber are two planar,metallic, electrodes 50 and 51, preferably constructed of aluminum whichmay be coated with insulating aluminum oxide. The gap 52 between theelectrodes, 50 and 51, is adjustable by virtue of the movable bottomelectrode 50. Terminals A and B are connected to the electrodes via aninsulating feedthrough 48. The outer end of these terminals may beconnected to an RF source (not shown) in such a way that when terminal Bis connected to a ground potential, terminal A must be connected to theRF source, or vice versa, providing for an electrical symmetricalconfiguration. The work load to be sterilized is placed on bottomelectrode 50.

It is important to maintain the distance between the electrodes alwayssmaller than the distance of the RF-powered electrode's edge to thegrounded chamber's wall. This enables a well defined and intense plasmaglow to be confined to space 52 between the electrodes and preventsdeleterious sparking. The electrode material may also be made of theperforated stock previously mentioned. However, it is desirable to havethe RF-powered electrode made of solid stock to enable water-cooling ofthat electrode. The bottom electrode may also be made of solid stock toenable a cool surface upon which the work load to be sterilized will beplaced. This chamber will commonly be evacuated to 10 microns Hg beforegas introduction via the perforated gas diffusion tubes 35. Practicaldevice sterilization can be obtained with process parameters for gasflow rates in the range 20 to 1000 scc/m, corresponding to a totalsterilization reaction pressure of 10-1000 microns Hg, at a range of RFpower densities of 0.0125 to 0.05 W/cm³.

FIG. 7 illustrates in diagrammatic form yet another preferred embodimentfor practicing the process of the invention. The outer wall of chamber21 is again formed of metal, such as aluminum or stainless steelmaintained at ground potential, and is of similar dimensions to thatillustrated in FIG. 3. Mounted within the chamber is a single planar,metallic, electrode 50, preferably constructed of aluminum which may becoated with insulating aluminum oxide to reduce RF sputtering. Thiselectrode is commonly connected to an RF source in the MHz range andcarries the work load to be sterilized. This electrode has commonly atotal surface area which is at least four times smaller than the totalinternal surface area of the chamber.

This electrical configuration is usually referred to as asymmetric andis conducive to generating an extremely uniform plasma glow filling theentire volume of the process chamber. It is also responsible for thedevelopment of a characteristic accelerating potential at the surface ofelectrode 50, associated with a thin "dark space" through which positiveplasma ions will accelerate and impinge on the electrode and the workload it normally carries.

The main advantage of this configuration is its ability to renderefficient sterilization at relatively low power densities in the rangeof 0.0125 -0.025 W/cm³. This configuration is also easily scalable as afunction of work load size and its configuration.

This process chamber commonly operates with at least an order ofmagnitude lower pressure than the pressure for chambers described inFIGS. 1 through 6, while the gas dispersion tubes 35 are similar inconstruction to those previously mentioned. To prevent RF sputtering ofelectrode 50 due to positive ion bombardment, it may either behard-anodized or alternatively aluminum oxide spray-coated.

One particular sub-configuration to that described in FIG. 7 isillustrated in FIG. 8. In this configuration a metallic perforatedenclosure 51 totally surrounding and containing electrode 50 may beused, and connected to a separate RF source 22a. This perforatedenclosure may be equipped with an open/close hinging mechanism (notshown) to enable access for material to be sterilized to be placed onelectrode 50 contained within enclosure 51. This yields the beneficialeffect of being able to separately control the abundance of sterilizingactive species and their impinging energy. RF power applied to electrode50, which may or may not include a negative DC potential from a separateDC supply, (not shown), will control energy of ion impingement, while RFpower applied to the auxiliary perforated enclosure will control activespecies abundance.

With this configuration, RF power sources operating at 100 KHz and 13.56MHz may be used in the various possible permutations. Interestingresults are obtained by mixing both frequencies while being applied to asingle element. Commonly, one frequency has to be applied at a higherpower fraction, usually around 90% of the total applied power to thesame element. Such interesting process results were obtained when thetwo different frequencies were mixed and applied to electrode 50 in theabsence of any auxiliary perforated enclosure. The mixed frequencyconcept also lends itself to low power density sterilization in therange 0.0125 to 0.025 W/cm³, with the advantage of maintaining theoverall temperature relatively low (below 50° C.), particularly whenelectrode 50 is water-cooled.

It is worth noting that the auxiliary perforated enclosure ought to beof high mesh transparency to allow the plasma glow to extend past it andcontact electrode 50. Best operating conditions will be obtained for thesmallest surface area of this perforated metallic enclosure.

FIG. 9 illustrates diagrammatically a preferred embodiment forpracticing the process of the invention under atmospheric pressureconditions in ambient air. In this configuration no vacuum capability isrequired. Material to be sterilized is placed via material loading means67 on grounded conveyor belt 62 which sweeps the load across thedischarge gap created between conveyor belt 62 and RF-powered electrode61. The material is removed from conveyor belt 62 by any conventionalunloading means 68. The powered electrode produces a large plurality ofneedle-like discharges, which create individual discharge sparks towardthe counter grounded electrode 62. The larger the gap between theelectrodes, the higher the power needed to initiate the discharge inair.

Sterilization is effected due to ozone formation following the dischargeof oxygen in the ambient air. Power density requirements in the range 5to 15W/cm² are not uncommon. Maintaining a controlled relative humidityof 50 to 60% in the discharge gap will facilitate initiation of thedischarge and promote atomic oxygen generation. The latter serves as aprecursor to ozone formation, the final desired sterilant in thisconfiguration.

Ozone toxicity inhibits wide acceptance of such a corona discharge inair for the purpose of medical device sterilization. Alternatively,therefore, the RF-powered electrode 61 may assume a configurationcomprised of multiple open nozzles 65, capable of dispersing oxidizinggases immediately adjacent to conveyor belt 62. In this configurationthe discharge would still be created in ambient air, however thedispersion through the open nozzles 65 of a judiciously selected feedgas will increase the local concentration of its active species 63relative to that of ozone. In this manner, sterilization would beattributable to active species derived from any feed gas introduced intothe hollow RF-powered electrode 61 and not to the deleterious ozone gas.

The dispersing nozzles 65 may assume different configurations. Forexample, separate nozzle tubes may be inserted into a hollow section ofelectrode block 61, which may or may not be of different material thanelectrode block 61. These tubes may also be screwed into electrode block61 for easy replacement. A typical hole size for each individual nozzleis in the range 0.015-0.040".

The advantages of this discharge configuration are mainly in terms ofsystem simplicity and in the context of continuous operation, coupledwith the ability to easily change the residence time of a work loadwithin the discharge gap.

Disadvantages are commonly associated with erosion and degradation ofboth electrode block 61 and conveyor belt 62. Electrode 61 should beconstructed from oxidation-resistant materials (e.g., tungsten,molybdenum or alloys thereof). Conveyor belt 62 ought to be resistant toelectrical punch-through and be constructed from fluorinated, orfluorinated/chlorinated hydrocarbons (e.g., DuPont products). Highmelting polyimides or Kalrez-like synthetics may serve as alternateconstruction materials for the conveyor belt. Kalrez is a polyimidemanufactured by DuPont.

Set forth below are specific examples of suitable operating parametersfor effective sterilization employing an apparatus as illustrated inFIG. 1 where the outer chamber wall is formed of quartz glass. Theseresults were achieved with a chamber 8" ID. by 8" long. In some examplesoperation included the metallic perforated cylinders as indicated in theembodiments of FIG. 3 and 4 to provide device sterilization in afield-free and glowless operation. In others the configuration waswithout such shielding internal cylinders.

For each of the examples the general technique involved was one in whichthe material to be sterilized was placed within a Tyvek bag which itselfwas sealed and placed in a wire basket within the chamber.

The materials used for verification of sterilization effectiveness were"Attest" vials obtained from 3M Company, each vial contained a bacterialstrip having an original spore population of not less than 1×10⁶Bacillus subtilis var Niger per strip. The strips contained in thepermeable plastic vials were not brought into contact with the culturesolution contained in any of the vials. The vials prior to sterilizationwere placed within the Tyvek bags during the plasma sterilization.

For each example the chamber was first evacuated to an initial lowpressure level after the materials (in the bags or pouches) were placedwithin the wire basket in the chamber. The chamber was thereafter filledwith the appropriate gas prior to striking the discharge, and the gascontinued to flow through the chamber at a controlled rate to establisha steady state sterilization pressure. The discharge was initiated bythe application of RF power as indicated. The discharge was maintainedfor a controlled time period at the end of which the chamber was firstevacuated, then backfilled with air and later opened and the samplesremoved. The temperature within the chamber during the process wasmaintained at less than 60° C.

Subsequent to the tests the spore strips were submitted to anindependent testing laboratory which performed a total plate count onthe sample strips using a procedure in which 100 milliliters of steriledeionized water were added to each strip in a sterile whirl-pak bag. Thebag was then placed in a lab blender for 10 minutes. One 10 milliliteraliquot of sample, a duplicate one milliliter sample, and twoconsecutive 10⁻¹ dilutions were plated using Tryptic Soy Agar. Theplates were then incubated at 30°-35° C. for 72 hours. After incubation,the plates were read and recorded, and the results calculated on aColony Forming Unit (CFU) basis.

EXAMPLE 1 (Without internal shield cylinder)

Gas: O₂ (Pure)

Flowrate: 24 scc/min

Pressure: 0.3 torr

Power Density: 0.045W/cm³

Exposure time: 30 min.

Resultant microbial count: <10 CFU (below sensitivity limit of countingtechnique)

Percent kill: 99.9999%

EXAMPLE 2 (Without internal shield cylinder)

Gas: O₂ (Pure)

Flowrate: 125 scc/min

Pressure: 0.8 torr

Power Density: 0.03W/cm³

Exposure time: 30 min.

Resultant microbial count: <10 CFU (below the sensitivity limit ofcounting technique)

Percent kill: 99.9999%

EXAMPLE 3 (Without internal shield cylinder)

Gas: O₂ /CF₄ (8%)

Flowrate: 32 scc/min

Pressure: 0.3 torr

Power Density: 0.027W/cm³

Exposure time: 30 min.

Resultant microbial count: <10 CFU (below the sensitivity limit ofcounting technique)

Percent kill: 99.9999%

EXAMPLE 4 Field-Free Operation (Employing Shielding Perforated Cylinder)

Gas: O₂ /CF₄ (8%)

Flowrate: 32 scc/min

Pressure: 0.3 torr

Power Density: 0.027W/cm³

Exposure time: 30 min.

Resultant microbial count: <20 CFU (at the sensitivity limit of countingtechnique)

Percent kill: 99.9999%

EXAMPLE 5 (Without internal shield cylinder)

Gas: He(59.85%)-O₂ (39.90%) - CF₄ (0.25%)

Flowrate: 45 scc/min

Pressure: 0.35 torr

Power Density: 0.030W/cm³

Exposure time: 30 min.

Resultant microbial count: <10 CFU

Percent kill: 99.9999%

EXAMPLE 6 (Without internal shield cylinder)

Gas: He(59.85%)-O₂ (39.90%) - CF₄ (0.25%)

Flowrate: 44 scc/min

Pressure: 0.35 torr

Power Density: 0.019W/cm³

Exposure time: 60 min.

Resultant microbial count: <10 CFU

Percent kill: 99.9999%

EXAMPLE 7 (Without internal shield cylinder)

Gas: O₂ (60%)-He(40%)

Flowrate: (total) 47 scc/min

Pressure: 0.35 torr

Power Density: 0.030W/cm³

Exposure time: 30 min.

Resultant microbial count: <10 CFU

Percent kill: 99.9999%

EXAMPLE 8 (Without internal shield cylinder)

Gas: O₂ (pure)

Flowrate: 25 scc/min

Pressure: 0.3 torr

Power Density: 0.015W/cm³

Exposure time: 55 min.

Resultant microbial count: <10 CFU

Percent kill: 99.9999%

EXAMPLE 9 Field-Free Operation (Employing Shielding Perforated Cylinder)

Gas: O₂ (pure)

Flowrate: 49 scc/min

Pressure: 0.45 torr

Power Density: 0.038W/cm³

Exposure time: 60 min.

Resultant microbial count: <10 CFU

Percent kill: 99.9999%

Having described the specific process and apparatus of the invention asdefined by the below appended claims.

I claim:
 1. Apparatus for sterilization of medical devices and materialsin a substantially continuous process in a gas plasma at or nearatmospheric pressure comprising:a first electrode suitable to form acorona discharge in a gas at or near atmospheric pressure, a secondgenerally planar electrode, an RF power source connected between saidfirst electrode and said planar electrode capable of producing a powerdensity in ambient air of at least 5 Watts/cm², and a conveyor meanspositioned in close contact with said planar electrode for substantiallycontinuously carrying said material to be treated through the dischargegap between the electrodes at or near atmospheric pressure, saidconveyor means including means for loading said material to be treatedonto said conveyor means before it is carried through said discharge gapand for unloading said material from said conveyor means after it hasbeen carried through said discharge gap.
 2. Apparatus in accordance withclaim 1 wherein said first electrode is partially hollow and containsmultiple open nozzles capable of dispersing gas into the discharge gapbetween the electrodes and further including,means for supplying a gasto said gas dispersing nozzles.
 3. Apparatus in accordance with eitherclaim 1 or 2 wherein said first electrode is formed from the group ofmaterials including tungsten, molybdenum or alloys thereof.
 4. Apparatusin accordance with either claim 1 or 2 wherein said conveyor means isformed from a selected one of the group of high melting point and highdielectric strength materials consisting of, fluorinatednitrogen-containing hydrocarbons, fluorinated/chlorinatednitrogen-containing hydrocarbons.